Tumor radiosensitivity predicted by 18F-FLT PET imaging
CHEN Zhong-jie, ZHANG Bai-lin, TIAN Gang, XU Wen-gui
Published 2013-01-25
Cite as Chin J Nucl Med Mol Imaging, 2013,33(01): 60-64. DOI: 10.3760/cma.j.issn.2095-2848.2013.01.016
Abstract
Objective To evaluate if 18F-FLT PET imaging could be used as a new clinical method to predict tumor radiosensitivity.Methods MDA-MB-231 and LN229 cells were irradiated with doses of 0,8 and 16 Gy of 6 MV photon energy,then soft agar assay and cellular uptake of 18F-FLT were performed on the 2 cell lines.The t test and one-way analysis of variance were used for the two groups and data before and after irradiation.The MDA-MB-231 and LN229 tumor xenografts were prepared by injecting the tumor cells into the right limbs of female BALB/c nu/nu mice.Once tumors reached a diameter of 10 mm,the two types of mice were divided randomly into 3 groups (20 mice per group) according to the irradiation doses (0,8 and 16 Gy).After irradiation,18F-FLT PET imaging and immunohistochemical staining were conducted.Then correlations between 18F-FLT SUVtumor/SUVmuscle ratio (T/M ratio) and TK1 labeling index percentages (LITK1) were tested using linear correlation analysis.Results The survival fraction of MDA-MB-231 and LN229 cells after irradiated with 8 Gy were (59.73 ± 4.3) % and (93.41 ± 3.75) %,respectively (t =-13.20,P < 0.001).When the dose increased to 16 Gy,the survival fraction decreased to (43.57 ±4.06) % and (81.77 ± 4.42) %,respectively(t =-14.24,P < 0.001).In MDA-MB-231 cells,the cellular uptake of 18F-FLT after irradiation with 8 Gy declined rapidly to (18.32 ± 1.38) kBq/105 cells ((128.22 ± 8.24) kBq/105 cells with the dose of 0 Gy,F =266.41,P < 0.01),and maintained this low level till 72 h.For the LN229 cells,the cellular uptake decreased to (9.87 ± 1.30) kBq/105 cells after 8 Gy irradiation ((134.88 ± 6.59) kBq/105 cells with the dose of 0 Gy,F =346.06,P < 0.01),then increased gradually to (127.17 ± 9.08) kBq/105 cells at 72 h (F =346.06,P > 0.05).The dynamic changes of 18F-FLT cellular uptake in the two cells had the same pattern after being treated with 16 Gy irradiation.In the 18F-FLT PET image of MDA-MB-231 tumor mice after 8 Gy radiotherapy,the T/M ratio decreased to 0.78 ± 0.39 at the first day,but it was 2.84 ± 0.29 before radiotherapy (F =39.78,P <0.01).Then the ratio increased slowly,and it was still lower than the baseline at 7 d after radiation (F =39.78,P <0.01).The same pattern could be seen in the group of 16 Gy irradiation.In LN229 tumor mice treatment with 8 Gy irradiation,the T/M ratio increased to 2.41 ±0.47 at the first day,and it was 1.58 ±0.29 before radiotherapy (F =34.01,P < 0.05).The ratio decreased steadily to 0.66 ± 0.32 (F =34.01,P<0.05) at 7 d after radiotherapy.However,in the treatment group with 16 Gy,the T/M ratio decreased gradually and reached 0.44 ± 0.22 at 7 d (F =41.85,P < 0.01).A correlation was found between 18F-FLT T/M ratio and LITK1 (8 Gy:r=0.67,0.73; 16 Gy:r=0.73,0.69; all P<0.01) in both tumor models.Conclusion 18F-FLT PET imaging may be used as a new assay to predict tumor radiosensitivity,but further investigation is needed before clinical application.
Key words:
Breast neoplasms; Glioma; Tumor cell, cultured; Radiotherapy; Tomography,emission-computed; Thymidine; Mice, nude
Contributor Information
CHEN Zhong-jie
Department of Radiotherapy, Tianjin Cancer Institute and Hospital,Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
ZHANG Bai-lin
Department of Radiotherapy, Tianjin Cancer Institute and Hospital,Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
TIAN Gang
Department of Radiotherapy, Tianjin Cancer Institute and Hospital,Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
XU Wen-gui
Department of Radiotherapy, Tianjin Cancer Institute and Hospital,Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China